A Comparison of Chromosome Repair Kinetics in G0 and G1 Reveals that Enhanced Repair Fidelity under Noncycling Conditions Accounts for Increased Potentially Lethal Damage Repair
A Comparison of Chromosome Repair Kinetics in G0 and G1 Reveals that Enhanced Repair Fidelity under Noncycling Conditions Accounts for Increased Potentially Lethal Damage Repair
复制标题
DOI：
10.1667/rr2159.1
复制
发表时间：
2010-11-01
影响因子：
3.4
通讯作者：
Ito, Hisao
中科院分区：
文献类型：
--
作者：
Liu, Cuihua;Kawata, Tetsuya;Ito, Hisao
本研究通过分析受6戈伊照射后处于非周期G（0）期或进入G（1）期的细胞染色体断裂、重接和错接的动力学，研究了融合的人成纤维细胞的潜在致死性损伤（PLD）及其修复。将病毒介导的早熟染色体凝聚（PCC）技术与荧光原位杂交（FISH）技术相结合，研究间期染色体畸变。流式细胞术显示，绝大多数细胞在从G（0）释放后15 h尚未进入S期。到这个时候，大约95%的最初产生的过早凝聚的染色体断裂已经重新连接，表明大多数修复过程发生在G（1）。对于每种培养条件，过早凝聚的染色体断裂的重新连接动力学是相似的。然而，在非循环条件下，错误修复的峰值为0.55次交换/细胞，而在循环条件下（G（1）），它的峰值为1.1次交换/细胞。在辐射后12小时，循环细胞（G（1））的复合物型交换比非循环细胞（G（0））多7倍。由于G（0）/G（1）中的大多数修复通过非同源末端连接（NHEJ）过程发生，因此增加的PLD修复可能是由于NHEJ途径的改善的细胞周期特异性重新连接保真度。(C)2010年，辐射研究学会
Potentially lethal damage (PLD) and its repair were studied in confluent human fibroblasts by analyzing the kinetics of chromosome break rejoining and misrejoining in irradiated cells that were either held in noncycling G(0) phase or allowed to enter G(1) phase of the cell cycle immediately after 6 Gy irradiation. Virally mediated premature chromosome condensation (PCC) methods were combined with fluorescence in situ hybridization (FISH) to study chromosomal aberrations in interphase. Flow cytometry revealed that the vast majority of cells had not yet entered S phase 15 h after release from G(0). By this time some 95% of initially produced prematurely condensed chromosome breaks had rejoined, indicating that most repair processes occurred during G(1). The rejoining kinetics of prematurely condensed chromosome breaks was similar for each culture condition. However, under noncycling conditions misrepair peaked at 0.55 exchanges per cell, while under cycling conditions (G(1)) it peaked at 1.1 exchanges per cell. At 12 h postirradiation, complex-type exchanges were sevenfold more abundant for cycling cells (G(1)) than for noncycling cells (G(0)). Since most repair in G(0)/G(1) occurs via the non-homologous end-joining (NHEJ) process, increased PLD repair may result from improved cell cycle-specific rejoining fidelity of the NHEJ pathway. (C) 2010 by Radiation Research Society